N-Linked glycosylation is an essential eukaryotic protein modification. An oligosaccharide consisting of 14 sugar residues is synthesized at the endoplasmic reticulum (ER) membrane before being transferred to a protein (Kornfeld and Kornfeld 1985; Varki 1996; Burda and Aebi 1999). Dolichol phosphate is used as a lipid carrier for the synthesis, which is initiated by the addition of phospho-GlcNAc forming GlcNAc- pyrophosphate-dolichol (GlcNAc-PP-Dol). This is followed, in order, by additions of another GlcNAc, nine mannose, and three glucose residues. On the cytoplasmic side of the ER, activated sugars (UDP-GlcNAc and GDP-Man) are the donors for the two GlcNAc and first five mannose additions, respectively. The Man5GlcNAc2-PP-Dol is then translocated across the membrane into the ER lumen, where dolichol-phosphate- mannose-dependent mannosyltransferases sequentially add four mannose residues. (For further information on Dol-P-Man, see Chapter 78). The synthesis is completed by the transfer of three glucose residues from Dol-P-Glc to the oligosaccharide. (For a description of Dol-P-Glc-dependent transferases, see Chapter 82). The Glc3Man9GlcNAc2 oligosaccharide is transferred to nascent glycoproteins by the oligosaccharyltransferase complex (see Chapter 83).
KeywordsKiller Toxin Mannose Residue Endoplasmic Reticulum Lumen ALC3 Gene Dolichol Phosphate
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- Cipollo JF, Trimble RB (2000) The accumulation of Man(6)GlcNAc(2)-PP-dolichol in the Saccharomyces cerevisiae Δalg9 mutant reveals a regulatory role for the Alg3p α1,3-Man middle-arm addition in downstream oligosaccharide-lipid and glycoprotein glycan processing. J Biol Chem 275:4267–4277PubMedCrossRefGoogle Scholar
- Huffaker TC, Robbins PW (1981) Temperature-sensitive yeast mutants deficient in asparagine-linked glycosylation. J Biol Chem 257:3203–3210Google Scholar
- Kurzik-Dumke U, Kaymer M, Gundacker D (1997) Gene within a gene configuration and expression of the Drosophila melanogaster genes lethal(2) neighbour of tid [1(2)not] and lethal (2) relative of tid. Genetics 200:45–58Google Scholar
- Orlean P (1994) DPM1. In: Book Rothblatt J, Novick P, Stevens T (eds) Guidebook to the secretory pathway. Oxford University Press, Oxford, pp 54–56Google Scholar
- Rush J, Waechter CJ (1998) Topological studies on the enzymes catalyzing the biosynthesis of Glc-P-dolichol and the triglucosyl cap of Glc3Man9GlcNAc2-P-P-dolichol in microsomal vesicles from pig brain: use of the processing glucosidases I/II as latency markers. Glycobiology 8:1207–1213PubMedCrossRefGoogle Scholar